Efficacy and Safety of IgPro10 in Adults With Systemic Sclerosis (SSc)
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Interventions
- Biological: IgPro10Biological: Placebo
- Registration Number
- NCT04138485
- Lead Sponsor
- CSL Behring
- Brief Summary
This randomized, multicenter, double-blind (DB), placebo controlled, phase 2 study will evaluate the efficacy and safety of IgPro10. The DB Treatment Period will be followed by a 24-week Open-label (OL) Treatment Period.
Eligible subjects will be randomized at Baseline in a 2:1 ratio of treatment IgPro10 or placebo in the DB Treatment Period. All subjects who enter OL Treatment Period will receive IgPro10.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
-
- Age ≥18 years (male or female) at time of providing written informed consent
- Documented diagnosis of SSc according to ACR / EULAR criteria 2013
- mRSS ≥ 15 and ≤ 45
- Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation
- Subjects within first 18 months of disease duration from first non-Raynaud's phenomenon manifestation.
- Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, and dermatomyositis, as determined by the investigator Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy or myositis at Screening are not excluded
- Positive anti-centromere autoantibodies at Screening
- Evidence of severe chronic kidney disease with estimated glomerular filtration rate < 45 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) or receiving dialysis. Additionally, subjects with current confirmed diagnosis of diabetes mellitus and requiring medication, with eGFR < 90 mL/min/1.73m2 will be excluded from the study.
- History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary
- Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation
- Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden)
- Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess)
- Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year
- Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L)
- Known IgA deficiency or serum IgA level < 5% lower limit of normal
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IgPro10 IgPro10 10% liquid formulation of human immunoglobulin for intravenous use Placebo Placebo 0.5% human albumin solution stabilized with 250 mmol/L L-proline
- Primary Outcome Measures
Name Time Method Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo Over 48 weeks
- Secondary Outcome Measures
Name Time Method Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events Over 48 weeks Proportion of responders (ACR CRISS > 0.6) Over 72 weeks Mean change from Baseline in Modified Rodnan Skin Score (mRSS) Baseline and over48 weeks Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Baseline and over 72 weeks Mean change from Baseline in Forced Vital Capacity (FVC)% predicted Baseline and over 72 weeks Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted Baseline and over 72 weeks Mean change from Baseline in Physician Global Assessment (MDGA) Baseline and over 72 weeks Mean change from Baseline in Patient Global Assessment (PGA) Baseline and over 48 weeks PGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor)
Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale Baseline and over 48 weeks This survey consists of 34 questions and items are scored on a scale of 0 (better health) to 3 (worse health). Scores are combined to form total score.
Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo Baseline and up to 48 weeks Proportion of responders in mRSS Up to 48 weeks Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo
Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo Over 48 weeks Treatment failure - defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all-cause mortality
Proportion of subjects with events at Week 48 in IgPro10 vs Placebo Over 48 weeks Events defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all -cause mortality
Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo Baseline and over 48 weeks Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo Baseline and over 48 weeks Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo Baseline and over 48 weeks Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) Over 72 weeks Percentage of subjects with AEs, TEAEs, SAEs, AESIs Over 72 weeks Concentration of serum trough IgG levels at Baseline and prior to first infusion Baseline and up to 72 weeks Mean change from Baseline in Modified Rodnan skin score (mRSS) Baseline and over 72 weeks Mean change from Baseline in Patient global assessment (PGA) Baseline and over 72 weeks
Trial Locations
- Locations (77)
Louisiana State University Health Sciences Center
🇺🇸Shreveport, Louisiana, United States
Rutgers Clinical Research Center
🇺🇸New Brunswick, New Jersey, United States
Boston University Amyloidosis Center
🇺🇸Boston, Massachusetts, United States
University of California
🇺🇸Los Angeles, California, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Lombardi Cancer Center-Georgetown University
🇺🇸Washington, District of Columbia, United States
Pacific Arthritis Care Center
🇺🇸Los Angeles, California, United States
Alliance for Multispecialty Research
🇺🇸Wichita, Kansas, United States
John Hopkins Bayview Medical Center
🇺🇸Baltimore, Maryland, United States
Hospital Italiano de Buenos Aires
🇦🇷Buenos Aires, Argentina
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Altoona Center For Research
🇺🇸Duncansville, Pennsylvania, United States
The University Of Texas Medical School At Houston (Utms)
🇺🇸Houston, Texas, United States
UZ Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
John Hunter Hospital / Autoimmune Resource and Research Centre
🇦🇺New Lambton Heights, New South Wales, Australia
CHU de Caen
🇫🇷Caen, France
CHRU de Lille Hopital Huriez
🇫🇷Lille Cedex, France
Kerckhoff Klinik GmbH, Abteilung für Rheumatologie und Klinische Immunologie Rheumatologie
🇩🇪Bad Nauheim, Germany
CHU Hautepierre
🇫🇷Strasbourg, France
Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)
🇩🇪Berlin, Germany
Centre Hospitalier Universitaire de Rouen-Hopital
🇫🇷Rouen cedex, France
University Hospital Of Tuebingen
🇩🇪Tuebingen, Germany
Modena University
🇮🇹Modena, Italy
Uniwersytecki Szpital Kliniczny W Bialymstoku
🇵🇱Bialystok, Poland
Hospital Universitari Materno Infantil Vall Dhebron
🇪🇸Barcelona, Spain
Universita degli Study di Ancona
🇮🇹Ancona, Italy
Universita Degli Studi Di Bari Aldo Moro
🇮🇹Bari, Italy
Azienda Ospedaliera Gaetano Pini
🇮🇹Milano, Italy
Universita degli Studi di Napoli Federico II
🇮🇹Napoli, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
🇮🇹Rome, Italy
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Mayo Clinic Arizona - Scottsdale
🇺🇸Scottsdale, Arizona, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Heartland Research Associates, LLC
🇺🇸Wichita, Kansas, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Mount Sinai Hospital, The Rebecca Macdonald Centre For Arthritis
🇨🇦Toronto, Canada
University of Pennsylvania - Perelman Center
🇺🇸Philadelphia, Pennsylvania, United States
Northwell Health
🇺🇸Great Neck, New York, United States
APRILLUS Asistencia e Investigacion Clinica
🇦🇷Buenos Aires, Argentina
Sanatorio Parque S.A y Consultorios Externos Asociados
🇦🇷Rosario, Argentina
Internal Medicine, Nantes University Hospital
🇫🇷Nantes, France
CHU de Rennes-Hopital Sud
🇫🇷Rennes, France
Assistance Publique - Hopitaux de Paris (AP-HP)
🇫🇷Paris, France
Universitaetsklinikum Freiburg- Klinik fuer Rheumatologie und Klinische Immunologie
🇩🇪Freiburg, Germany
Charite - Universitaetsmedizin Berlin - Campus Charite Mitte
🇩🇪Berlin, Germany
Universitaetsmedizin der Johannes Gutenberg
🇩🇪Mainz, Germany
Universita degli Studi Di Brescia
🇮🇹Brescia, Italy
Universita degli Studi Firenze
🇮🇹Firenze, Italy
UOC Immunoreumatologia
🇮🇹L'Aquila, Italy
University Hospital of Cologne
🇩🇪Köln, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Centro de Investigacion y Tratamiento Reumatologico S.C.
🇲🇽Ciudad de México, Mexico
Centro Integral en Reumatologia, SA de CV
🇲🇽Guadalajara, Mexico
Centro De Estudios De Investigation Basica Y Clinica S.C
🇲🇽Jalisco, Mexico
Cliditer, S.A. DE C.V.
🇲🇽Mexico City, Mexico
Instituto Nacional De Ciencias Medicas Y Nutricion
🇲🇽Mexico, Mexico
Centro de Alta Especialidad en Reumatologia
🇲🇽San Luis Potosi, Mexico
Klinika i Poliklinika Układowych Chorób Tkanki Łącznej Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji
🇵🇱Warszawa, Poland
Complejo Hospitalario Universitario A Coruna
🇪🇸A Coruna, Spain
University Clinical Centre, Medical University of Gdansk
🇵🇱Gdańsk, Poland
Samodzielny Publiczny Szpital Kliniczny
🇵🇱Katowice, Poland
Klinika Dermatologii Szpital im. Dzieciątka Jezus
🇵🇱Warszawa, Poland
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Royal Free Hospital-Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Countess of Chester Hospital
🇬🇧Chester, United Kingdom
Hospital Univ 12 de Octubre
🇪🇸Madrid, Spain
Hospital Infanta Luisa Quirónsalud
🇪🇸Sevilla, Spain
Hospital Universitari Dr.Peset
🇪🇸Valencia, Spain
Cantonal Hospital St. Gallen - Klinik fuer Rheumatologie
🇨🇭Saint Gallen, Switzerland
Chapel Allerton Hospital
🇬🇧Leeds, United Kingdom
PARC Clinical Research
🇦🇺Adelaide, South Australia, Australia
Cleveland Clinic - Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Hospital For Special Surgery
🇺🇸New York, New York, United States
Hospital St. Josef
🇩🇪Wuppertal, Germany
Hospital Militar Central
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina